Identification of candidate IgG biomarkers for Alzheimer’s disease via combinatorial library screening.

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Cell. 2011 Jan 7;144(1):132-42. doi: 10.1016/j.cell.2010.11.054.

Identification of candidate IgG biomarkers for Alzheimer’s disease via combinatorial library screening.

Source

Opko Health Laboratories, Jupiter, FL 33458, USA.

Abstract

The adaptive immune system is thought to be a rich source of protein biomarkers, but diagnostically useful antibodies remain unknown for a large number of diseases. This is, in part, because the antigens that trigger an immune response in many diseases remain unknown. We present here a general and unbiased approach to the identification of diagnostically useful antibodies that avoids the requirement for antigen identification. This method involves the comparative screening of combinatorial libraries of unnatural, synthetic molecules against serum samples obtained from cases and controls. Molecules that retain far more IgG antibodies from the case samples than the controls are identified and subsequently tested as capture agents for diagnostically useful antibodies. The utility of this method is demonstrated using a mouse model for multiple sclerosis and via the identification of two candidate IgG biomarkers for Alzheimer’s disease.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID:
21215375
[PubMed – indexed for MEDLINE]
PMCID:
PMC3066439

Free PMC Article

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Calorie restriction: what recent results suggest for the future of ageing research.

Eur J Clin Invest. 2010 May;40(5):440-50. doi: 10.1111/j.1365-2362.2010.02276.x.

Calorie restriction: what recent results suggest for the future of ageing research.

Source

Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA. dsmithjr@uab.edu

Abstract

BACKGROUND:

Calorie Restriction (CR) research has expanded rapidly over the past few decades and CR remains the most highly reproducible, environmental intervention to improve health and extend lifespan in animal studies. Although many model organisms have consistently demonstrated positive responses to CR, it remains to be shown whether CR will extend lifespan in humans. Additionally, the current environment of excess caloric consumption and high incidence of overweight/obesity illustrate the improbable nature of the long-term adoption of a CR lifestyle by a significant proportion of the human population. Thus, the search for substances that can reproduce the beneficial physiologic responses of CR without a requisite calorie intake reduction, termed CR mimetics (CRMs), has gained momentum.

MATERIAL AND METHODS:

Recent articles describing health and lifespan results of CR in nonhuman primates and short-term human studies are discussed. Additional consideration is given to the rapidly expanding search for CRMs.

RESULTS:

The first results from a long-term, randomized, controlled CR study in nonhuman primates showing statistically significant benefits on longevity have now been reported. Additionally, positive results from short-term, randomized, controlled CR studies in humans are suggestive of potential health and longevity gains, while test of proposed CRMs (including rapamycin, resveratrol, 2-deoxyglucose and metformin) have shown both positive and mixed results in rodents.

CONCLUSION:

Whether current positive results will translate into longevity gains for humans remains an open question. However, the apparent health benefits that have been observed with CR suggest that regardless of longevity gains, the promotion of healthy ageing and disease prevention may be attainable.

PMID:
20534066
[PubMed – indexed for MEDLINE]
PMCID:
PMC3073505

Free PMC Article

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The promise of dietary restriction mimetics in healthy aging

Biofactors. 2010 Sep-Oct;36(5):377-82. doi: 10.1002/biof.127.

Life span extension by resveratrol, rapamycin, and metformin: The promise of dietary restriction mimetics for an healthy aging.

Source

UMR, CNRS Université Lyon, Centre Léon Bérard, France.

Abstract

Life expectancy at the turn of the 20th century was 46 years on average worldwide and it is around 65 years today. The correlative increase in age-associated diseases incidence has a profound public health impact and is an important matter of concern for our societies. Aging is a complex, heterogeneous, and multifactorial phenomenon, which is the consequence of multiple interactions between genes and environment. In this review, we survey animals models that have been of great help for both investigating mechanism of aging and identifying molecules, which slow down the onset of age-related diseases. Resveratrol (RSV) is one of those. We will report evidences supporting RSV as a molecule that acts by mimicking the beneficial effects of dietary restriction, and may share common downstream targets with rapamycin and metformin. Although those molecules do not reveal all the secrets of the fountain of youth, they may help us maintaining the quality of life in the old age.

© 2010 International Union of Biochemistry and Molecular Biology, Inc.

PMID:
20848587
[PubMed – indexed for MEDLINE]
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Traumatic brain injury may be an independent risk factor for stroke

Traumatic brain injury may be an independent risk factor for stroke

  1. James F. Burke, MD, MS,
  2. Jessica L. Stulc, MD, MPH,
  3. Lesli E. Skolarus, MD, MS,
  4. Erika D. Sears, MD, MS,
  5. Darin B. Zahuranec, MD, MS and
  6. Lewis B. Morgenstern, MD

+Show Affiliations

| + Show Full Disclosures

  1. Correspondence to Dr. Burke: jamesbur@umich.edu
  1. Neurology July 2, 2013 vol. 81 no. 1 33-39

Abstract

Objective: To explore whether traumatic brain injury (TBI) may be a risk factor for subsequent ischemic stroke.

Methods: Patients with any emergency department visit or hospitalization for TBI (exposed group) or non-TBI trauma (control) based on statewide emergency department and inpatient databases in California from 2005 to 2009 were included in a retrospective cohort. TBI was defined using the Centers for Disease Control definition. Our primary outcome was subsequent hospitalization for acute ischemic stroke. The association between TBI and stroke was estimated using Cox proportional hazards modeling adjusting for demographics, vascular risk factors, comorbidities, trauma severity, and trauma mechanism.

Results: The cohort included a total of 1,173,353 trauma subjects, 436,630 (37%) with TBI. The patients with TBI were slightly younger than the controls (mean age 49.2 vs 50.3 years), less likely to be female (46.8% vs 49.3%), and had a higher mean injury severity score (4.6 vs 4.1). Subsequent stroke was identified in 1.1% of the TBI group and 0.9% of the control group over a median follow-up period of 28 months (interquartile range 14–44). After adjustment, TBI was independently associated with subsequent ischemic stroke (hazard ratio 1.31, 95% confidence interval 1.25–1.36).

Conclusions: In this large cohort, TBI is associated with ischemic stroke, independent of other major predictors.

Footnotes

via Traumatic brain injury may be an independent risk factor for stroke.

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Vitamin D and risk of death from vascular and no… [Eur Heart J. 2013] – PubMed – NCBI

Eur Heart J. 2013 May;34(18):1365-74. doi: 10.1093/eurheartj/ehs426. Epub 2012 Dec 20.

Vitamin D and risk of death from vascular and non-vascular causes in the Whitehall study and meta-analyses of 12,000 deaths.

Source

Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, UK.

Abstract

AIMS:

To examine the independent relevance of plasma concentrations of 25-hydroxyvitamin D [25(OH)D] for vascular and non-vascular mortality.

METHODS AND RESULTS:

We examined associations of plasma concentrations of 25(OH)D and cause-specific mortality in a prospective study of older men living in the UK and included findings in meta-analyses of similar studies identified by a systematic search reporting on vascular and all-cause mortality. In a 13-year follow-up of 5409 men (mean baseline age 77 years), 1358 died from vascular and 1857 from non-vascular causes. Median season-adjusted baseline 25(OH)D concentration was 56 (interquartile range: 45-67) nmol/L. After adjustment for age and seasonality, higher concentrations of 25(OH)D were inversely and approximately linearly (log-log scale) associated with vascular and non-vascular mortality throughout the range 40-90 nmol/L. After additional adjustment for prior disease and cardiovascular risk factors, a doubling in 25(OH)D concentration was associated with 20% [95% confidence interval (CI): 9-30%] lower vascular and 23% (95% CI: 14-31%) lower non-vascular mortality. In meta-analyses of prospective studies, individuals in the top vs. bottom quarter of 25(OH)D concentrations had 21% (95% CI: 13-28%) lower vascular and 28% (95% CI: 24-32%) lower all-cause mortality.

CONCLUSIONS:

Despite strong inverse and apparently independent associations of 25(OH)D with vascular and non-vascular mortality, causality remains uncertain. Large-scale randomized trials, using high doses of vitamin D, are required to assess the clinical relevance of these associations.

KEYWORDS:

Cardiovascular disease, Mortality, Vitamin D

via Vitamin D and risk of death from vascular and no… [Eur Heart J. 2013] – PubMed – NCBI.

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